Fluorescent handpiece

ABSTRACT

A handpiece can treat biological tissue using electromagnetic radiation, which can be substantially fluorescent light. The handpiece includes a source of electromagnetic radiation and a waveguide. The waveguide is adjacent the source, receives electromagnetic radiation from the source, and delivers the electromagnetic radiation to the biological tissue. The handpiece also includes a system for moving a fluorescent substance through the waveguide. The fluorescent substance includes a fluid base and a fluorescing agent and is capable of modulating at least one property of the electromagnetic radiation. A method is described for removing the fluorescing agent from the fluorescing substance and replacing it with a second, different fluorescing agent.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation-in-part of U.S. applicationSer. No. 13/361,748, filed Jan. 30, 2012, which is a continuation ofU.S. application Ser. No. 13/153,702, filed Jun. 6, 2011, now U.S. Pat.No. 8,105,369, which is a continuation of U.S. application Ser. No.12/014,989, filed Jan. 16, 2008, now U.S. Pat. No. 7,955,367, all ofwhich are expressly incorporated by reference in their entirety. Thepresent application claims priority to U.S. Application Nos. 61/447,654,filed Feb. 28, 2011, and 61/513,394, filed Jul. 29, 2011, both of whichare expressly incorporated by reference in their entirety.

BACKGROUND

1. Field

The invention relates generally to apparatuses and methods for treatingbiological tissue using electromagnetic radiation. In particular, theinvention relates to a fluorescent handpiece for treating biologicaltissue.

2. Description of the Related Art

Certain treatments for cosmetic and dermatologic conditions include theuse of non-coherent fluorescent light or intense pulsed light. Forexample, devices can include a fluorescent substance or dye fortransforming a first predetermined wavelength band of light to a secondpredetermined pulsed wavelength band of light, a first light source forproducing light including said first predetermined wavelength band, anda waveguide for directing said second predetermined pulsed wavelengthband to a predetermined location. Unfortunately, the efficacy of the dyecan suffer from quenching, bleaching, and other chemical reactions.Also, because the fluorescent substance or dye is heated duringoperation, and because heating can limit the useful lifetime of the dye,such devices can address the heating of the fluorescent substance ordye. For example, the dye can be circulated through a separate baseunit, to mitigate quenching, bleaching, and other chemical reactions, orto cool the dye in an attempt to extend its useful lifetime. However,the volume of circulating dye can be large and the system required tostore, pump, and circulate the dye can be large. Due to the volume ofdye and the size of the system, these components are generally in a baseunit separate from the treatment handpiece.

SUMMARY OF THE INVENTION

The invention, in various embodiments, relates to apparatuses andmethods for treating matter, for example, biological tissue usingelectromagnetic radiation. The biological tissue can be human skin,which can exhibit at least one of superficial vascular lesion, port winestain, telangiectasia, spider angioma, cherry angioma, rosacea,“diffusive red,” poikiloderma, post-operative bruising, venous lakessmall vessel diameter lesion, arterial lesion, capillary lesion, venouslesion, pigmented lesions (e.g., benign epidermal pigmented lesions,benign pigmented dermal lesions, Becker's nevus or acquired nevus ofHori), tattoos and other dermatological indications such as acne,psoriasis, vitiligo, and the like. The invention can also be used totreat wrinkles, for skin rejuvenation, for fat removal, for cellulite,for body sculpting, for decreasing circumference of a particular bodypart, for hair removal, and for hair regrowth. The devices and methodsdescribed herein can also be used for other scientific, industrial, orother non-therapeutic purposes.

Apparatuses can include fluorescent handpieces that include a source ofelectromagnetic radiation, a nonlinear waveguide, and a system forcirculating or passing a fluorescent substance through the nonlinearwaveguide. Advantages of the invention can include an apparatus that canbe smaller, less expensive, easier to handle, easier to store, moreefficient, and more robust than prior art sources of electromagneticradiation. The apparatus can also produce electromagnetic radiation ofat least partially enhanced or different parameters compared topreviously known apparatuses. Other advantages of the invention caninclude extending the usable lifetime of the fluorescent substance by atleast one of mitigating quenching of the fluorescent substance,mitigating bleaching of the fluorescent substance, mitigating heating ofthe fluorescent substance, and mitigating chemical reaction of thefluorescent substance. Additionally, the devices described hereinutilize fluorescent light rather than laser light. The fluorescentsubstance can advantageously be non-toxic, allowing for easier and saferhandling compared to laser dyes, which can be significantly toxic. Thedevices described herein also reduce risks to eye safety as compared tolaser systems and intense pulsed light sources.

In one aspect, the invention features a handpiece for treatingbiological tissue. The handpiece includes a source of electromagneticradiation, a nonlinear waveguide and a system for circulating afluorescent substance through the nonlinear waveguide. The nonlinearwaveguide is adjacent the source, receives electromagnetic radiationfrom the source, and delivers modulated electromagnetic radiation to thebiological tissue. The fluorescent substance is capable of modulating atleast one property of the electromagnetic radiation.

In one aspect, the invention features a handpiece for treatingbiological tissue. The handpiece is configured to receiveelectromagnetic radiation from at least one remote associated source ofelectromagnetic radiation, e.g. a crystal laser or a laser diode, via adelivery system for delivering the electromagnetic radiation to thehandpiece. Such a delivery system can be, e.g., a light guide such as anoptical fiber or an optical fiber bundle or a waveguide, for example, aliquid or partially liquid waveguide or hollow waveguide. The handpieceis configured to receive electromagnetic radiation from the at least oneremote associated source of electromagnetic radiation and a system forcirculating a fluorescent substance through the nonlinear waveguide. Thefluorescent substance is capable of modulating at least one property ofthe electromagnetic radiation.

In another aspect, the invention features an apparatus for treatingbiological tissue. The apparatus includes a base unit, an energy sourceassociated with the base unit, and an umbilicus. The umbilicus has afirst end associated with the base unit and a conduit for transmittingenergy from the energy source to a second end of the umbilicus. Theapparatus also includes a handpiece associated with the second end ofthe umbilicus. The handpiece includes a source of electromagneticradiation, a nonlinear waveguide, and a system for circulating orpassing a fluorescent substance through the nonlinear waveguide. Thesource is adapted for receiving energy from the energy source throughthe conduit. The nonlinear waveguide is adjacent the source, receiveselectromagnetic radiation from the source, and delivers modulatedelectromagnetic radiation to the biological tissue. The fluorescentsubstance is capable of modulating at least one property of theelectromagnetic radiation.

In still another aspect, the invention features a method of treatingbiological tissue. The method includes (i) providing electromagneticradiation to a nonlinear waveguide associated with a handpiece; (ii)circulating or passing a fluorescent substance through the nonlinearwaveguide to modulate at least one property of the electromagneticradiation; and (iii) delivering the modulated electromagnetic radiationto treat the biological tissue.

In other examples, any of the aspects above, or any apparatus or methoddescribed herein, can include one or more of the following features.

In various embodiments, the source can be selected from the groupconsisting of a flash lamp, a xenon flashlamp, a krypton flash lamp, axenon-krypton flash lamp, an arc lamp, a diode, a diode laser, laser,and an incoherent light source. In one embodiment, the handpieceincludes a coating associated with the nonlinear waveguide for enhancingemission of the electromagnetic radiation from the handpiece.

In some embodiments, the handpiece includes a pump within the system forcirculating or passing the fluorescent substance through the nonlinearwaveguide. In one embodiment, the handpiece includes a system forcooling the fluorescent substance. The handpiece can include a portadjacent the system, the port in fluid communication with the system andadapted for receiving the fluorescent substance. The handpiece caninclude a port that is adapted for receiving the fluorescent substancefrom a reservoir cartridge, the reservoir cartridge detachablyconnectable with the port.

In certain embodiments, the handpiece includes a reflector adjacent adistal end of the nonlinear waveguide, the reflector for reflectinglight to a proximal end of the nonlinear waveguide for delivery to thebiological tissue. In one embodiment, the modulated electromagneticradiation delivered to the biological tissue is substantiallyfluorescent light. The system can extend the usable lifetime of thefluorescent substance by at least one of mitigating aggregation of thefluorescent substance, mitigating quenching of the fluorescentsubstance, mitigating bleaching of the fluorescent substance, mitigatingheating of the fluorescent substance, and mitigating chemical reactionof the fluorescent substance.

In various embodiments, the handpiece includes a connector adjacent afirst portion of the handpiece, for connecting the handpiece to anumbilicus and for receiving energy from a conduit in the umbilicus, theenergy for driving the source of electromagnetic radiation. In oneembodiment, the connector is adapted to receive a fluorescent substancefrom the umbilicus and is in fluid communication with the system forcirculating or passing the fluorescent substance through the nonlinearwaveguide.

In some embodiments, the electromagnetic radiation delivered to thebiological tissue can be characterized by a pulse width between about0.5 ms and about 500 s. In some embodiments, the electromagneticradiation delivered to the biological tissue can be characterized by atissue exposure time in the range of about 500 ms to about 60 minutes.In one embodiment, the electromagnetic radiation delivered to thebiological tissue is absorbed preferentially by hemoglobin in blood overadjacent skin tissue. A spectrum characterizing the electromagneticradiation delivered to the biological tissue can be matched to anabsorption spectrum of at least one of whole blood, hemoglobin, reducedhemoglobin, and oxidized hemoglobin. The electromagnetic radiationdelivered to the biological tissue can be characterized by a spot sizeof about 2 mm or greater in diameter.

In certain embodiments, modulating at least one property of theelectromagnetic radiation can include varying at least one of awavelength, fluence, pulse or pulse train width (e.g., duration), pulseor pulse train shape, and exposure time of the tissue associated withthe electromagnetic radiation. In one embodiment, the electromagneticradiation delivered to the biological tissue is characterized by anenergy density between about 0.1 J/cm² and about 500 J/cm².

In various embodiments, the handpiece includes a skin contacting portionadjacent the waveguide for contacting the biological tissue anddelivering the electromagnetic radiation to the biological tissue. Inone embodiment, the handpiece includes a controller for tuning at leastone of a pulse width characterizing the electromagnetic radiationdelivered to the biological tissue and a fluence.

In some embodiments, the apparatus includes a port associated with thehandpiece and a cartridge containing the fluorescent substancedetachably connectable to the port, the cartridge providing thefluorescent substance to the system. In one embodiment, the apparatusincludes a reservoir for the fluorescent substance, the reservoirassociated with the base unit and in fluid communication with thesystem, through the umbilicus, for providing the fluorescent substanceto the system. The handpiece can be detachable from the umbilicus. Thebase unit can be detachable from the umbilicus.

In certain embodiments, the method includes treating skin having atleast one of a superficial vascular lesion, port wine stain,telangiectasia, spider angioma, cherry angioma, rosacea, “diffuse red,”poikiloderma, post-operative bruising, venous lakes, small vesseldiameter lesion, arterial lesion, capillary lesion, venous lesion,pigmented lesion (e.g., benign epidermal pigmented lesions, benignpigmented dermal lesions, Becker's nevus or acquired nevus of Hori),tattoo, acne, psoriasis, wrinkles, cellulite, and vitiligo, or the like.The method can also or alternatively include treating skin for skinrejuvenation, fat removal, body sculpting, decreasing circumference of abody part, hair removal, or hair regrowth. In one embodiment, the methodincludes delivering the electromagnetic radiation to the biologicaltissue in a train of pulses to gradually heat a region of the biologicaltissue to be treated. In another embodiment, the method includesdelivering the electromagnetic radiation to the biological tissue in atrain of pulses to first heat a region of the biological tissue to betreated to a predetermined temperature and second to maintain the regionof the biological tissue to be treated at about the predeterminedtemperature. The electromagnetic radiation can have varying pulse trainwidths and/or shapes. Modulating at least one property of theelectromagnetic radiation can include varying at least one of a lightdirection, wavelength, and fluence.

In some embodiments, a light-emitting, therapeutic system configured totreat biological tissue comprises a source of electromagnetic radiationand a waveguide positioned to receive electromagnetic radiation from thesource. The waveguide comprises first and second ends, and a wallextending therebetween, the wall configured to at least partiallytransmit the electromagnetic radiation therethrough, the wall defining apassage extending along a direction between said first and second ends,a fluorescent substance flowable within the passage, the fluorescentsubstance comprising a liquid base and a fluorescing agent, and an firstport and an second port in fluid communication with the passage. Thesystem further comprises an optical output element near one of the firstand second ends of the waveguide. The fluorescent substance isconfigured to absorb at least a portion of the electromagnetic radiationfrom the source through the wall and generate fluorescent light inresponse to the electromagnetic radiation. The waveguide is configuredto guide the fluorescent light emitted by the fluorescent substancetowards the optical output element by internally reflecting at least aportion of the fluorescent light, and the optical output element isconfigured to direct at least a portion of the fluorescent light towardsbiological tissue. The system also comprises a fluid conduit in fluidcommunication with the first and second ports and configured to carrythe fluorescent substance between the waveguide's passage and a fluidmoving system, the fluid moving system adapted to move the fluorescentsubstance from the first end to the second end through the passage andfrom the second end back to the first end through the fluid conduit, anda fluorescing agent removal device configured to be coupled to the fluidconduit and to remove the fluorescing agent from the fluorescentsubstance, the fluid conduit being configured to direct the fluorescentsubstance through the fluorescing agent removal device during a firstmode of operation and to bypass the fluorescing agent removal deviceduring a second mode of operation.

In some embodiments, the source is selected from the group consisting ofa flash lamp, a xenon flash lamp, a krypton flash lamp, a xenon-kryptonflash lamp, an arc lamp, a laser, a diode, and an incoherent lightsource. In some embodiments, the system further comprises a coolingsystem for cooling the fluorescent substance. In some embodiments, thesystem further comprises a fluid input port in fluid communication withthe fluid conduit and adapted to detachably connect to a reservoircartridge, the reservoir cartridge configured to supply the fluorescentsubstance. In some embodiments, the system further comprises a reflectornear the end opposite the optical output element end of the waveguide,the reflector configured to reflect the fluorescent light towards theoptical output element end of the waveguide for delivery to thebiological tissue via the optical output element. In some embodiments,the system further comprises a reflector extending around and spacedapart from the outside surface of the waveguide, the reflectorconfigured to reflect the fluorescent light towards the wall of thewaveguide. In some embodiments, the system further comprises a baseunit, an umbilicus connectable to the base unit, and a handpiececonnectable to the umbilicus, wherein the source, waveguide, and opticaloutput element are located within the handpiece In some embodiments, thesystem further comprises a base unit, an umbilicus connectable to thebase unit, and a handpiece connectable to the umbilicus, wherein thesource is located within the base unit and the waveguide and opticaloutput element are located within the handpiece, the umbilicuscomprising an optical conduit configured to transmit optical energy fromthe source to the waveguide.

In some embodiments, the fluorescent light delivered to the biologicaltissue is characterized by a pulse width between about 0.2 ms and about500 s. In some embodiments, a spectrum characterizing the fluorescentlight delivered to the biological tissue is matched to an absorptionspectrum of at least one of whole blood, hemoglobin, reduced hemoglobin,or oxidized hemoglobin. In some embodiments, the fluorescent lightdelivered to the biological tissue is characterized by a spot size ofabout 2 mm or greater in diameter. In some embodiments, the fluorescentlight delivered to the biological tissue is characterized by an energydensity between about 0.1 J/cm² and about 500 J/cm². In someembodiments, a spectrum characterizing the fluorescent light deliveredto the biological tissue is matched to an absorption spectrum of atleast one of melanin, porphyrin, exogenous pigment, fat, and water inthe biological tissue.

In some embodiments, the system further comprises a controller fortuning one or more of a pulse width and fluence characterizing thefluorescent light delivered to the biological tissue. In someembodiments, the system further comprises a cooling fluid flow path atleast part of which is configured to circulate cooling fluid between thewaveguide and the source of electromagnetic radiation. In someembodiments, the fluorescing agent removal device comprises a filter.The filter can comprise a deionization filter, a polarity filter, or aparticle filter. In some embodiments, the fluorescent substance furthercomprises an additive. The additive can be selected from a groupconsisting of one or more of the following: a solubility enhancingagent, a passive absorber, a fluorescent dye lifetime enhancing agent, adetergent, or a substance configured to change the polarity of thefluorescent substance. The additive can be configured to change aproperty of the fluorescent substance, wherein the property is selectedfrom a group consisting of one or more of the following: absorptionwavelength bandwidth, absorption wavelength bandwidth position in theelectromagnetic spectrum, emission wavelength bandwidth position in theelectromagnetic spectrum, emission wavelength bandwidth, absorption peakwavelength, emission peak wavelength, absorption efficacy, emissionefficacy, Stokes shift, fluorescent dye lifetime, proticity, whethersolution is more or less protic or aprotic, whether solution will let goof hydrogen bound to primarily oxygen in a solution, or polarity offluorescent substance.

In some embodiments, the fluorescing agent removal device is furtherconfigured to remove the additive from the fluorescent substance. Insome embodiments, the liquid base comprises one or more of: water, asolvent, an organic solvent, an alcohol, methanol, and ethanol. In someembodiments, the system further comprises a dye source in fluidcommunication with the fluid conduit, the dye source configured tocontain at least a portion of the fluorescent substance. The dye sourcecan be selected from the group consisting of one or more of thefollowing: a dye reservoir, a pellet, a tablet, a dye cartridge, a wetdye cartridge, a dry dye cartridge, a solution, a powder, a dye liquid,a receptacle, an ion exchange filter, an ion release filter, and acarbon filter.

In some embodiments, the system further comprises the fluid movingsystem, a base unit, an umbilicus connectable to the base unit, and ahandpiece connectable to the umbilicus, wherein the fluid moving systemis located within the handpiece. In some embodiments, the system furthercomprises the fluid moving system, a base unit, an umbilicus connectableto the base unit, and a handpiece connectable to the umbilicus, whereinthe fluid moving system is located within the base unit. In someembodiments, the system further comprises the fluid moving system,wherein the fluid moving system is configured to pump the fluorescentsubstance through the waveguide in a first mode from the first port tothe second port and in a second mode from the second port to the firstport. The fluid moving system can be configured to reverse the flow ofthe fluorescent substance through the fluid conduit in response to afluid flow control signal. The fluid moving system can comprise a fluidcirculation system configured to circulate the fluorescent substancethrough the waveguide.

In some embodiments, the fluorescing agent comprises a single dye andthe fluorescent light comprises a single emission peak. In someembodiments, the fluorescing agent comprises two or more dyes and thefluorescent light comprises two or more emission peaks. At least two ofthe emission peaks can at least partially overlap.

In some embodiments, the system further comprises a cooling system influid communication with the fluid conduit and configured to cool thefluorescent substance. The system can further comprise a handpiece,wherein the cooling system is located within the handpiece. The systemcan further comprise a base unit, wherein the cooling system is locatedwithin the base unit. The cooling system can be selected from the groupconsisting of one or more of: a thermoelectric cooler, a heat exchange,and a fan.

In some embodiments, the optical output element is selected from thegroup consisting of one or more of the following: a spacer, a positivetapered waveguide, a negative tapered waveguide, a waveguide havingdifferent surface areas at its proximal and distal ends, a waveguidehaving different shapes at its proximal and distal ends, a bifurcatedwaveguide, a multi-furcated waveguide, a fiber bundle, a fiber bundlehaving a larger surface area at its output end than at its input end, aplurality of apertures, an aperture, a solid light guide, a liquid lightguide, a hollow light guide, and a fiber. In some embodiments, thesystem further comprises a solid rod located within the waveguide, thesold rod configured to generate fluorescent light in response to theelectromagnetic energy.

In some embodiments, a method of generating fluorescent light forscientific or industrial use comprises providing a light-emitting systemadapted to generate fluorescent light for scientific or industrial use.The light-emitting system can comprise a waveguide positioned to receiveelectromagnetic energy from an electromagnetic energy source. Thewaveguide can comprise first and second ends, and a wall extending atleast partially therebetween, the wall configured to transmit theelectromagnetic radiation therethrough and defining a passage extendingalong a direction between said first and second ends, a fluorescentsubstance flowable within the passage, the fluorescent substanceconfigured to absorb the electromagnetic radiation and generatefluorescent light in response to the electromagnetic radiation, thefluorescent substance comprising a liquid base and a fluorescing agent,and an input port and an output port in fluid communication with thepassage. The light-emitting system can further comprise an opticaloutput element near one of the first and second ends of the waveguide,and a fluid conduit in fluid communication with the input and outputports.

The method can further comprise circulating the fluorescent substancefrom the first end to the second end through the passage and from thesecond end back to the first end through the fluid conduit, transmittingelectromagnetic radiation through the wall of the waveguide to thefluorescent substance within the passage, guiding at least some of thefluorescent light emitted by the fluorescent substance in response tothe electromagnetic radiation through the waveguide towards the opticaloutput element, removing the fluorescing agent from the fluorescentsubstance by directing the fluorescent substance through a fluorescingagent removal device, and providing an additional quantity of the samefluorescing agent to the liquid base.

In some embodiments, the fluorescing agent removal device comprises adeionization filter. In some embodiments, providing an additionalquantity of the fluorescing agent comprises adding a tablet, pellet,powder, or solution of dye to the liquid base. The liquid base cancomprise water. In some embodiments, providing comprises manually addingthe fluorescing agent to the liquid base. In some embodiments, themethod can further comprise sensing a depletion of the fluorescing agentand activating an indicator in response to said sensing. In someembodiments, the method can further comprise sensing a depletion of thefluorescing agent and automatically adding additional fluorescing agentin response to said sensing.

In some embodiments, a method of generating fluorescent light forscientific or industrial use comprises providing a light-emitting systemadapted to generate fluorescent light for scientific or industrial use.The light-emitting system can comprise a waveguide positioned to receiveelectromagnetic energy from an electromagnetic energy source. Thewaveguide can comprise first and second ends, and a wall extending atleast partially therebetween, the wall configured to transmit theelectromagnetic radiation therethrough and defining a passage extendingalong a direction between said first and second ends, a fluorescentsubstance flowable within the passage, the fluorescent substanceconfigured to absorb the electromagnetic radiation and generatefluorescent light in response to the electromagnetic radiation, thefluorescent substance comprising a liquid base and a first fluorescingagent, and an input port and an output port in fluid communication withthe passage. The light-emitting system can further comprise an opticaloutput element near one of the first and second ends of the waveguideand a fluid conduit in fluid communication with the input and outputports.

The method can further comprise moving the fluorescent substance fromthe first end to the second end through the passage and from the secondend back to the first end through the fluid conduit, transmittingelectromagnetic radiation through the wall of the waveguide to thefluorescent substance within the passage, guiding at least some of thefluorescent light emitted by the fluorescent substance in response tothe electromagnetic radiation through the waveguide towards the opticaloutput element, the fluorescent light having a first peak wavelength,removing the fluorescing agent from the fluorescent substance bydirecting the fluorescent substance through a fluorescing agent removaldevice, and providing a second fluorescing agent to the liquid baseafter said removing, the second fluorescing agent being different thanthe first fluorescing agent.

In some embodiments, the second fluorescing agent is configured togenerate light having a second peak wavelength that is different fromsaid first peak wavelength. In some embodiments, removing comprisesdirecting the fluorescent substance through a deionization filter. Insome embodiments, removing comprises directing the fluorescent substancethrough a polarity filter. In some embodiments, providing an additionalquantity of the fluorescing agent comprises adding a tablet, pellet,powder, or solution of dye to the liquid base. The liquid base cancomprise water. In some embodiments, providing comprises manually addingthe fluorescing agent to the liquid base.

In some embodiments, the method further comprises sensing a depletion ofthe fluorescing agent and activating an indicator in response to saidsensing. In some embodiments, the method further comprises receiving aninput to change the wavelength of the fluorescent light and performingsaid removing and providing a second fluorescing agent in response tosaid input.

Other aspects and advantages of the invention will become apparent fromthe following drawings and description, all of which illustrateprinciples of the invention, by way of example only.

BRIEF DESCRIPTION OF THE DRAWINGS

The advantages of the invention described above, together with furtheradvantages, may be better understood by referring to the followingdescription taken in conjunction with the accompanying drawings. Thedrawings are not necessarily to scale, emphasis instead generally beingplaced upon illustrating the principles of the invention.

FIG. 1 illustrates various aspects of a fluorescent handpiece.

FIG. 2 illustrates an exemplary arrangement of some aspects of afluorescent handpiece.

FIG. 3 illustrates another view of certain aspects of a fluorescenthandpiece.

FIG. 4 illustrates an embodiment of an apparatus for treating biologicaltissue.

FIG. 5 illustrates a method for treating biological tissue using afluorescent handpiece.

FIGS. 6A-D illustrate the exemplary embodiments of FIGS. 1-4, in 3Drenderings produced by CADD-type software.

FIG. 7 illustrates another embodiment of a system for treatingbiological tissue with fluorescent light.

FIG. 8 illustrates one embodiment of the dye removal system of FIG. 6.

FIG. 9 illustrates one embodiment of the cooling system of FIG. 6.

FIG. 10 illustrates one embodiment of the handpiece of FIG. 6.

FIG. 11 illustrates another embodiment of the waveguide system of thehandpiece of FIG. 9.

FIG. 12 illustrates an embodiment of a substantially cylindrical outputoptic.

FIG. 13 illustrates an embodiment of the output optic of FIG. 12 havingan optional flared end.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

FIG. 1 illustrates various aspects of a fluorescent handpiece 100 fortreating biological tissue using electromagnetic radiation. Thehandpiece 100 includes a source 105 of electromagnetic radiation and anonlinear waveguide 110 adjacent the source 105. The source 105 caninclude a cover 120 and can have a gas in its interior 125. The source105 can have positive 150 and negative 155 terminals, for establishing acircuit to deliver energy to drive the source 105. The waveguide 110 caninclude a pipe or flexible tube 130 and a passage 135 for a fluorescentsubstance. The handpiece 100 can include a system 115 for circulating afluorescent substance through the waveguide 110. The handpiece 100 canalso include a conduit 165 that establishes fluid communication betweenthe waveguide 110, the system 115, and a reservoir 160. Further, thehandpiece 100 can include a skin contacting portion 140 adjacent thewaveguide 110 and a reflector 170 adjacent a distal end of the waveguide110. Furthermore, the handpiece 100 can include at least one coolingsystem 145 in thermal communication with at least one of the source 105,the waveguide 110, and the system 115. In the illustrated embodiment,the cooling system 145 includes an intake 175 and an exhaust 180, forreceiving and removing coolant.

In various embodiments, the source 105 can be a flash lamp, a xenonflashlamp, a krypton flash lamp, a xenon-krypton flash lamp, an arclamp, a diode, and an incoherent light source. The handpiece 100, invarious embodiments, can include one, two, three, or more sources. Insome embodiments, pulses or pulse trains from the source 105 can berepeated at a frequency of about 0.2 to about 10 Hz. In some embodimentshaving more than one source 105, the sources can pulse simultaneouslywith single pulses or pulse trains or sequentially with overlapping,partially overlapping, or non-overlapping pulses. The waveguide 110receives electromagnetic radiation from the source 105 and deliverselectromagnetic radiation to the biological tissue (not shown). Thewaveguide 110 can include at least one of a glass, crystal, plastic,borosilicate, silicate, sapphire, poly methyl methacrylate (PMMA), PTFE,or any other suitable transparent material. The waveguide 110 caninclude a partial or complete coating or coatings for enhancing emissionof the electromagnetic radiation. For example, the coating can be atleast one of a metal, silica, silica-titania, tantala, organic material,PTFE, and a short pass optical coating. In one embodiment, the waveguide110 is a single tube waveguide adapted for containing a fluorescentsubstance. In other embodiments, a waveguide can be a co-axial waveguideadapted for separately containing two or more fluorescent substances.

The waveguide 110 can be adapted to deliver electromagnetic radiationdirectly to the biological tissue, or can be adapted to deliverelectromagnetic radiation to the biological tissue through a skincontacting portion 140 adjacent the waveguide 110. The skin contactingportion 140 can include a glass, a crystal, silica, sapphire, orplastic. The electromagnetic radiation delivered to the biologicaltissue can be substantially fluorescent light. In various embodiments,the handpiece 100 includes a reflector 170 adjacent a distal end of thewaveguide 110. The reflector 170 is adapted for reflecting light to aproximal end of the nonlinear waveguide for delivery to the biologicaltissue. In one embodiment, the reflector 170 is a mirror. In anotherembodiment, the reflector 170 is a diffusive white or off-white (e.g.,does not substantially absorb electromagnetic radiation) surface. Thereflector 170 can wrap around the waveguide 110 and/or the source 105,to increase the amount of electromagnetic radiation delivered to thewaveguide 110. The reflector 170 can be an ellipsis, a waveguide andsource close coupling cavity, or other geometrical shape selected tofocus and/or deliver electromagnetic radiation from the source 105 tothe waveguide 110.

In some embodiments, the waveguide 110 can be made of or coated with amaterial selected to have a refractive index lower than, higher than, orequal to a refractive index of the fluorescent substance. If thedifference between the refractive indices of the waveguide 110 and thefluorescent substance is large, light is bent more (the angle of thelight is changed to a greater extent) as it enters the waveguide 110wall and returns to the fluorescent substance from the waveguide 110wall than if the difference between the refractive indices of thewaveguide 110 and the fluorescent substance is smaller. A greater degreeof refraction or change in the angle of the light results in a greaterenergy loss. Therefore, a small difference between the refractiveindices of the waveguide 110 and the fluorescent substance can helpadvantageously reduce loss of light energy and enhance performance.Selecting materials so that the waveguide 110 has a lower refractiveindex than the fluorescent substance can also help reduce refraction,thereby reducing energy loss and increasing efficiency. In someembodiments, the lower the concentration of the fluorescent substance,the greater the impact of the difference in refractive indices betweenthe waveguide 110 and fluorescent substance on the amount of light lostand efficiency.

In some embodiments, the waveguide 110 can comprise a flexible tube orsleeve rather than a rigid tube made of, for example, glass. A diameterof a flexible waveguide 110 can change as the pressure of thefluorescent substance flowing through the waveguide 110 changes, similarto a balloon. A flexible material, for example, polytetrafluoroethylene(PTFE) can have a low index of refraction so that the waveguide 110 ismore efficient and produces more output energy. Example materials forthe waveguide 110, generally in order of decreasing refractive indicesand therefore decreasing loss of light energy, include: a glass, forexample LASF43 glass, sapphire, quartz, boro silicate, and AF-2400Teflon® (polytetrafluoroethylene (PTFE)). In some embodiments having awaveguide 110 with a high refractive index, the difference in therefractive indices of the waveguide 110 and fluorescent substance can bereduced by selecting a fluorescent substance having a high refractiveindex, e.g., polyethylene glycol or silicon oil. A fluorescent substancehaving a higher refractive index can also allow for more fluorescentlight to be captured in the waveguide 110 and fluorescent substance bymeans of total internal reflection, thereby amplifying light energywithin the waveguide 110.

FIG. 2 illustrates an exemplary arrangement of various aspects of afluorescent handpiece. In various embodiments, the waveguide 110 isseparated by a distance d1 from the source 105, which can mitigateheating of the waveguide 110 and the fluorescent substance by the source105 by mitigating the thermal communication between the source 105 andthe waveguide 110. The separation distance d1 can also mitigate heatingby facilitating a coolant, or other cooling element, to be disposed atleast partially between the source 105 and the waveguide 110. In oneembodiment, distance d1 can be about 1 mm to 100 mm, for example, 10 mm.In various embodiments, the waveguide 110 has a length l1, which can begreater than, less than, or equal to the length l2 of the source 105(e.g., arc length, excluding the dimension of the electrodes), which canfacilitate transmission of electromagnetic radiation to substantiallythe entire length of the waveguide 110 and/or maximize the use of thefluorescent substance. In one embodiment, length l1 can be about 1 mmshorter than the length l2 (e.g., 0.5 mm shorter at each end). In oneembodiment, length l1 can be about 2 mm to 4 mm shorter than the lengthl2 (e.g., 1 mm to 2 mm longer at each end). In some embodiments, thewaveguide length l1 can be greater than length l2 of the source 105. Forexample, the waveguide 110 can be sealed off and have an o-ring at eachend. The o-ring end portions can each be about 1 mm in length, so thatthe total waveguide 110 length l1 is about 2 mm greater than length l2.The end portions of the waveguide 110 can be coated with a reflective ortotally internally reflective coating to help reduce the loss of lightfrom the waveguide 110 to the o-rings and to protect the o-rings fromthermal damage. The coating can be, e.g., internal gold, internalsilver, an optical coating, PTFE, or another low refractive indexmaterial. In various embodiments, the waveguide 110 is separated by adistance d2 from the skin contacting portion 140. In one embodiment, thedistance d2 is about 0.5 mm. In various embodiments, the waveguide 110has a diagonal length (e.g., a diameter) 13 that is less than acorresponding diagonal length l4 of the skin contacting portion 140. Inone embodiment, length (e.g., a diameter) l4 is about two times distanced2 longer than length l3 (e.g., l4≈2d·2+l3), to direct the coneelectromagnetic radiation emitted from waveguide 110 to the skin.However, the lengths l4 and l3 are not limited to this relationship andcan be substantially the same, greater, or lesser.

In another embodiment, the waveguide 110 and the skin contacting portion140 are substantially in contact. In one embodiment, the waveguide 110and the reflector 170 are not in direct contact or are otherwiseseparated (e.g., intervened by a gas, liquid, or solid). This separationcan facilitate cooling of the waveguide 110, for example, by increasingthermal communication between the waveguide 110 and a coolant or othercooling element. In some embodiments, the fluorescent substance cancirculate or pass through the space between the waveguide 110 andreflector 170. This spatial separation can also be designed to optimizethe reflection of electromagnetic radiation from a distal end of thewaveguide 110, to the reflector 170, and back into the waveguide 110. Inanother embodiment, the waveguide 110 and the reflector 170 aresubstantially in contact. The relative positions, sizes, and/or opticalproperties (e.g., convexity/concavity/flatness) of the waveguide 110 andthe reflector 170 can be designed to maximize the amount ofelectromagnetic radiation reflected back into the waveguide.

The fluorescent substance can be circulated by the system 115 throughthe waveguide 110, and is capable of modulating at least one property ofthe electromagnetic radiation. The system 115 can help extend the usablelifetime of the fluorescent substance by at least one of mitigatingquenching of the fluorescent substance, mitigating bleaching of thefluorescent substance, mitigating heating of the fluorescent substance,and mitigating chemical reaction of the fluorescent substance. In someembodiments, the system 115 can include a particle filter. In someembodiments, the system 115 can be adjacent a port, which is in fluidcommunication with the system and adapted for receiving the fluorescentsubstance from a reservoir 160. In one embodiment, the port is adaptedfor receiving the fluorescent substance from a cartridge that isdetachably connectable with the port. A cartridge can contain about 2deciliters, or more, or less, of the fluorescent substance. In anotherexample, the port can be adapted for receiving the fluorescent substancefrom another source such as an umbilicus that can be attached to thehandpiece 100. A conduit 165 establishes a fluid communication betweenthe waveguide 110, the system 115, and the port.

The system 115 can include a pump for circulating the fluorescentsubstance. The pump can be any type of pump suitable for a fluorescentsubstance, including a bellows, centrifugal, diaphragm, drum, flexibleliner, flexible impeller, gear, peristaltic (e.g., tubing), piston,progressive cavity, rotary lobe, rotary vane, or syringe pump. In oneembodiment, the pump is a magnetically-coupled gear-type pump. Inanother embodiment, the pump is a solenoid operated pump. In variousembodiments, the pump can include a polytetrafluoroethylene (PTFE, forexample TEFLON®, a registered trademark of E. I. du Pont de Nemours andCompany) or a stainless steel material defining at least a portion of acirculation path of the fluorescent substance. PTFE, or a material withsimilar physical and chemical properties, can be used in the seals. Pumpmaterials can be selected that are essentially chemically inert, forexample, with respect to the fluorescent substance and the operatingenvironment.

FIG. 3 illustrates a cross sectional view 150 of a portion of thefluorescent handpiece of FIG. 1. The source 105 can include a cover 120and can have a gas in its interior 125. In one example, the gas isxenon. In general, the source 105 is selected to emit at least awavelength of light employed by the fluorescent substance. In oneembodiment, the passage 135 through the waveguide 110 has a diameter ofabout 2 mm to about 30 mm. In one embodiment, the thickness of the pipe130 wall can be in the range of about 0.5 mm to about 2 mm. In general,the passage 135 has a diameter that is selected to contain a sufficientvolume of fluorescent substance, the thickness of the pipe 130 wall isselected based upon the material to provide sufficient structuralintegrity, and the total diameter of the waveguide 110 is chosen withregard to the desired spot size to be produced by the handpiece 100. Thetotal diameter of the waveguide 110 can also be chosen with regard tothe dimensions of the source 105, the length of the waveguide 110, andthe concentration of the fluorescent substance.

In general, the fluorescent substance is capable of modulating (e.g.,transforming, converting, or varying) at least one property of theelectromagnetic radiation. For example, the fluorescent substance can bea dye selected to convert the electromagnetic radiation from at leastone first wavelength to at least one second wavelength. In someembodiments, more than one dye can be employed to utilize the light fromthe source 105. Accordingly, at least one dye can be selected dependingupon the desired treatment and/or desired emission wavelength. Becausethe emission wavelength can be controlled by selecting one or moreappropriate dyes, the fluorescent handpiece 100 does not require afilter to obtain the desired emission wavelength. However, in someembodiments, the fluorescent handpiece 100 can include a filter, forexample an optical filter, for controlling the wavelengths delivered tothe biological tissue. In some embodiments, a spatial filter is used tocontrol the spot size and spot shape.

The absorbing and emitting wavelengths of the fluorescent substance canbe selected by the user or a technician. In one example, the fluorescentsubstance can change blue-green light to yellow light. For example, thefluorescent substance can be a liquid dye such as pyrromethene, forexample, pyrromethene 556, for changing light emitted from the source105 to the desired wavelength. The concentration of the dye can bevaried to achieve different wavelengths of output light. A suitableconcentration can be a concentration sufficient to achieve about 70-100%absorption of electromagnetic bandwidth of the electromagnetic radiationfrom the source 105. The liquid base can be, for example, water, analcohol, e.g., polyethylene glycol, a mixture of alcohols, for example,methanol and/or ethanol, or a mixture of alcohol and water. Other liquidbases, for example, an oil, such as silicon oil, or DMSO, are alsopossible. In various embodiments, the fluorescent substance can include4-dicyanomethylene-2-methyl-6-(p(dimethylamino)styryl)-4H-pyran (DCM),pyrromethene, fluorescein, coumarin, stilbene, umbelliferone, tetracene,malachite green, rhodamin, rhodamin 6G, or Sulforhodamine 640 Chloride.In various embodiments, adamantine can be added to a fluorescentsubstance to prolong its life. In some embodiments, cycloheptatriene andcyclooctatetraene can be added to a fluorescent substance as tripletquencher, to increase output power. In certain embodiments, afluorescent substance can include one or more pyrromethenes or otherfluorescent dyes. The reflection index for the liquid can differstrongly from the reflection index in the waveguide 110, or can besubstantially the same. A suitable flow rate for the liquid can be about0.5-4 L/min. The passage 135 can be part of the system 115.

In various embodiments, the cooling system 145 can be a system forcooling the fluorescent substance. In some embodiments, the system 115for circulating a fluorescent substance can function as, or include a,system for cooling the fluorescent substance. The cooling system 145 canalso be adapted to cool any of the components of the handpiece 100,and/or to cool the biological tissue separately or in an integratedcooling system. The cooling system 145 can be in thermal communicationwith at least one of the source 105, the waveguide 110, the skincontacting portion 140, and the system 115. The cooling system 145 canemploy a coolant such as a gas or liquid to cool at least one of thesource 105, the waveguide 110, the skin contacting portion 140, and thesystem 115. In one embodiment, the cooling system 145 employs water as acoolant. In one embodiment, the cooling system 145 has an intake 175 andan exhaust 180, for receiving and removing coolant in the cooling system145. In one embodiment, the cooling system 145 includes a Peltier, orthermo-electric cooler. The cooling system 145 can include a radiator ora fan.

In some embodiments, various components of the system can benefit fromcooling, for example, the fluorescent substance, the source 105, and/orskin contacting portion 140 or output optic described in greater detailherein. Each of these components can have an associated cooling system,either separately or integrated with the others. The source 105 can beprovided with its own cooling system due to the amount of heat producedby the source 105. In some embodiments, a cooling system cools thefluorescent substance, which in turn can cool the skin contactingportion 140 or output optic. In some embodiments, the waveguide 110 canhave its own associated cooling system, for example, a water jacket. Thevarious cooling systems can include a radiator, a fan, a heat-exchangersystem, or any other cooling system described herein or otherwise knownin the art.

U.S. Pat. No. 5,320,618, the disclosure of which is incorporated hereinby reference in its entirety, teaches various sources, waveguides,systems, systems for cooling, and other aspects that can be readilyadapted by one skilled in the art for use with the present invention.

In various embodiments, the electromagnetic radiation delivered to thebiological tissue is characterized by a pulse width or exposure timebetween about 0.2 ms and about 60 min. In some embodiments, theelectromagnetic radiation delivered to the biological tissue can becharacterized by pulses of about 0.2 ms to about 500 ms with incrementsof about 0.2 ms. In some embodiments, a pulse width is between about 0.4ms and about 100 ms. In some embodiments, a pulse width is about 1, 2,3, 4, 5, 10, 15, or 20 s. The current system can produce light pulseshaving longer pulse widths than typical laser systems operating at thesame wavelength. For example, the pulse width of some dye lasers islimited by triplet state formation. Laser systems also disadvantageouslycan cause adverse effects such as purpura, pain, PIH (post inflammatoryhyperpigmentation), and/or revascularization. The electromagneticradiation delivered to the biological tissue can be absorbedpreferentially by a chromophore in the skin. For example, thechromophore can include at least one of hemoglobin in blood, melanin,pheomelanin, porphyrin, exogenous pigment, fat, and water in the skin.The chromophore can absorb the electromagnetic radiation preferentiallyover adjacent skin tissue. The spectrum characterizing theelectromagnetic radiation delivered to the biological tissue can bematched to an absorption spectrum of at least one of whole blood,hemoglobin, reduced hemoglobin, and oxidized hemoglobin.

For example, in some embodiments, the electromagnetic radiationdelivered to the biological tissue can have an intensity peak at awavelength of about 544 nm and a full width at half maximum of about 530nm to about 570 nm or about 529 nm to about 586 nm to approximate theabsorption spectrum of hemoglobin. Such a light spectrum canadvantageously be used to treat vascular lesions. One challenge intreating vascular lesions is the possibility of revascularization, whichcan cause treatment resistance and/or a need for multiple treatments.Revascularization can occur if endothelium is left not denaturized inthe tissue after treatment. Revascularization can be caused, at least inpart, by short pulses that explode the intima so that the vesselendothelium is not completely denaturized. Growth factors released aspart of an inflammatory response to the injury can cause the vessel tore-grow from the non-denaturized endothelium cells. Electromagneticpulses of more than 0.45 ms and up to 20 ms at the absorption bands ofhemoglobin can allow for selective destruction of a more completeportion of the endothelium of the vessel to be removed to help preventrevascularization.

In some embodiments, the concentration of the dye can be varied toachieve different wavelengths of output light. For example, a higherconcentration of pyromethene 556, for example, about 9.6 g/L, canproduce yellow light having an intensity peak of about 575 nm. Thefluorescent substance can also be selected to have a differentconcentration of a yellow emitting dye to produce green lightsubstantially without yellow wavelengths and having intensity peaks atabout e.g., 529 nm, 532 nm, or 535 nm. For example, a more dilutedsolution including pyromethene 556, for example, about 4.8 g/L, canproduce green light. The fluorescent substance can also be selected toproduce UVA, blue, orange, red, or NIR light. In some embodiments, asystem as described herein can allow the wavelength peak to be tuned towavelengths between about 450 nm and about 850 nm. In some embodiments,a system as described herein can allow the wavelength peak to be tunedto wavelengths between about 500 nm and about 670 nm. In someembodiments, the peaks can be overlapping or separate.

Electromagnetic radiation can also be delivered by scattering-depthdetermined deposition. For example, freckles of different shades (e.g.,light, medium, and dark relative to surrounding skin) can be treated bydifferent wavelengths of electromagnetic radiation (e.g., peaks of about480 nm for light, about 515 nm for medium, and about 535 nm for dark). Alight, shallow freckle may not have enough pigment to absorb enoughelectromagnetic radiation to be effectively treated. By using a shorterwavelength, electromagnetic radiation can scatter more in the tissue andpenetrate less through the tissue, which can result in a longer path andmore absorption within the freckle. In another example, a thicker,deeper (e.g. dermal) blood vessel can be treated by a relatively longerwavelength, which can reach within the dermis, and a thinner, shallowerblood vessel can be treated by a relatively shorter wavelength. In oneembodiment, a thicker vessel can be treated by electromagnetic radiationin the range of about 555-595 nm and a thinner vessel can be treated byelectromagnetic radiation in the range of about 515 to 555 nm. Foranother example, resistant port wine stains are often seen in infants orjuveniles with little melanin and are typically found in a shallowportion of the vessel bed. To treat such port wine stains, thewavelength of light delivered to the tissue can be selected to have ashorter wavelength so that the energy penetrates less and moreeffectively treats the shallow part of the juvenile port wine stain.

The electromagnetic radiation delivered to the biological tissue can becharacterized by a spot size between about 1 mm and about 40 mm. A spotsize can be up to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, or 20mm in diameter. In various embodiments, the handpiece can produce a spotsize of about 2 mm or greater in diameter. In general, the opticaldiameter of the waveguide and the skin contacting portion areproportional to the diameter of the spot size when the skin contactingportion is in contact with the skin. The spot can be various shapes, forexample, rectangular, quadratic, round, or elliptical. The spot size canbe changeable by means of, for example, an exchangeable extension of theskin contacting element, and/or an exchangeable spatial filter.

The electromagnetic radiation delivered to the biological tissue can becharacterized by an energy density between about 0.1 J/cm² and about 500J/cm². In various embodiments, the electromagnetic radiation deliveredto the biological tissue can be characterized by an energy densitybetween about 1 and about 100 J/cm², about 2.5 J/cm² and about 60 J/cm²,or about 2.5 J/cm² and about 20 J/cm². In certain embodiments, theenergy density can be about 1, 5, 10, 50, 100, 150, 200, 250, 300, 350,400, or 450 J/cm². In some embodiments with skin exposure time of longerthan about a few seconds can have fluences higher than 450 J/cm². Thehandpiece can include means for tuning a pulse width and/or fluencecharacterizing the electromagnetic radiation delivered to the biologicaltissue.

FIG. 4 illustrates an embodiment of an apparatus 200 for treatingbiological tissue. The apparatus 200 includes a fluorescent handpiece100 that can include the features described in connection with FIG. 1.The apparatus 200 also includes a base unit 210 that can include atleast one of an energy 205 source, a coolant 225 source, and acontroller 250. The base unit 210 can be connected to the fluorescenthandpiece 100 by an umbilicus 215. The umbilicus 215 includes a first240 point of connection between the umbilicus 215 and the handpiece 100,and a second 245 point of connection between the umbilicus 215 and thebase unit 210. The umbilicus 215 can include a power 220 conduit fortransmitting energy from the energy 205 source to the source 105 ofelectromagnetic radiation via a circuit established through the positive150 and negative 155 terminals. The umbilicus 215 can also include acoolant 230 conduit that establishes coolant communication between thefluorescent handpiece 100 and the base unit 210.

In various embodiments the cooling system 145 can cool the fluorescentsubstance and/or other components of the handpiece 100. The coolingsystem 145 can be adapted for cooling biological tissue. The base unit210 can include a coolant 225 source that can deliver coolant to thecooling system 145 through a coolant 230 conduit. The coolant 230conduit travels through (or along or on the outside of) the umbilicus tothe cooling system 145 via a delivery or circulatory system establishedthrough the intake 175 and, if necessary, an exhaust 180. In someembodiments the coolant 230 conduit facilitates coolant flow only to(e.g., in the case of a gas that can be vented) or both to and from(e.g., in the case of fluid that can be circulated) the handpiece 100.In certain embodiments, the coolant 225 source includes means to controland/or circulate the coolant, and the coolant 230 conduit and coolingsystem 145 are simply channels. In one embodiment, the cooling system145 can control and/or circulate the coolant. In one embodiment, theapparatus 200 includes a radiator or heat exchanger in the handpiece 100or the base unit 210.

In some embodiments, the apparatus 200 includes a controller 250 forcontrolling at least one of the energy 205 source, the coolant 225source, the cooling system 145, and the source 105.

FIG. 4 illustrates a first 240 point of connection between the umbilicus215 and the handpiece 100, and a second 245 point of connection betweenthe umbilicus 215 and the base unit 210. In some embodiments, thesepoints of connection are essentially fixed at the time of manufacture orassembly and are not detachable without specialized tools. However, invarious embodiments, these points of connection are easily and quicklydetachable and reattachable without specialized tools. In someembodiments, the first 240 point of connection is detachable andreattachable such that a practitioner or technician can easily andquickly change handpieces in a clinical situation. For example, theapparatus can also include a first connector associated with the secondend of the umbilicus and a second connector associated with thehandpiece, the second connector detachably connectable to the firstconnector. In various embodiments, the handpiece includes a connectoradjacent a first portion of the handpiece, for connecting the handpieceto an umbilicus and for receiving energy from a conduit in theumbilicus, the energy for driving the source of electromagneticradiation. The connector can be adapted to receive a fluorescentsubstance from the umbilicus and is in fluid communication with thesystem for circulating or passing the fluorescent substance through thenonlinear waveguide. This has the advantage of allowing multiplehandpieces to be used with a single base unit 210 and/or singleumbilicus 215. Likewise, in some embodiments, the second 245 point ofconnection is detachable and reattachable such that the base unit isdetachable from the umbilicus. U.S. patent application Ser. No.11/800,663, the disclosure of which is incorporated herein by referencein its entirety, teaches various detachable handpieces and connectorsthat can be readily adapted by one skilled in the art for use with thepresent invention.

FIG. 5 illustrates a method 400 for treating biological tissue using afluorescent handpiece. Step 405 includes providing electromagneticradiation to a nonlinear waveguide associated with a handpiece. Thehandpiece can include aspects described in connection with FIGS. 1-4.Step 410 includes circulating or passing a fluorescent substance throughthe nonlinear waveguide to modulate at least one property of theelectromagnetic radiation. Modulating at least one property of theelectromagnetic radiation can include varying at least one of awavelength, fluence, pulse or pulse train width, and pulse or pulsetrain shape associated with the electromagnetic radiation. Step 415includes delivering the modulated electromagnetic radiation to treat thebiological tissue.

In some embodiments, the method 400 includes treating skin having atleast one of a superficial vascular lesion, port wine stain,telangiectasia, spider angioma, cherry angioma, rosacea, “diffusivered,” poikiloderma, post-operative bruising, venous lakes, small vesseldiameter lesion, arterial lesion, capillary lesion, venous lesion,pigmented lesion (e.g., benign epidermal pigmented lesions, benignpigmented dermal lesions, Becker's nevus or acquired nevus of Hori),tattoo, acne, psoriasis, vitiligo, and the like. The method 400 can alsoinclude treatments for wrinkles, for skin rejuvenation, fat removal,cellulite, body sculpting, decreasing circumference of a body part, forhair removal, and for hair regrowth. In certain embodiments, the method400 includes delivering the electromagnetic radiation to the biologicaltissue in a train of pulses to gradually heat a region of the biologicaltissue to be treated.

FIGS. 6A-D illustrate the exemplary embodiments of FIGS. 1-4, in 3Drenderings produced by CADD-type software. The reference numbers inFIGS. 6A-D correspond to the elements discussed in connection with FIGS.1-4.

FIG. 7 illustrates another embodiment of a system 500 for treatingbiological tissue with fluorescent light. The system includes a baseunit 510 and a fluorescing handpiece 530. An umbilicus 540 connects thehandpiece 530 to the base unit 510. The base unit 510, handpiece 530,and umbilicus 510 are similar to, and include many of the same featuresas the base unit, handpiece and umbilicus described above with respectto FIGS. 1-5.

In the present embodiment, the base unit 510 includes a system, such asa dye pump 512, a dye reservoir 514, a dye removal system 700, a coolingsystem 750, a power supply 520 and a controller 522. The base unit 510may also include a user interface and safety interlock system (notshown). In some alternative embodiments, one or more of a dye pump 512,a dye reservoir 514, a dye removal system 700, a cooling system 750, apower supply 520 and a controller 522 can be located in the handpiece530.

The handpiece 530 includes an electromagnetic energy source 532 and awaveguide system 534. The umbilicus 540 includes electrical and fluidconduits to allow circulation or passing of dye and cooling fluid, anddelivery of electrical energy, from the base unit 510 to the handpiece530. In some embodiments, the electromagnetic energy source 532 islocated in the base unit 510, and the umbilicus 540 includes a deliverysystem, for example, a light guide such as an optical fiber, opticalfiber bundle, or a waveguide, for example, a liquid or partially liquidor hollow waveguide, or other means to transfer energy to the waveguidesystem 534 in the handpiece 530. In some embodiments, the source 532 canbe, for example, a laser, a green laser, a lamp, or a diode laser.

The dye reservoir 514 may include a tank in which a fluorescing dyesolution is stored. The dye solution may be formed by combining a dyepellet, powder, or liquid drops with a solvent, such as water. The dyesolution is formed as the dye pellet, powder or drops dissolve into thewater. In some embodiments, the dye reservoir 514 includes a device tofacilitate dye dissolution. For example, the dye reservoir 514 mayinclude a mixer or stirrer. In one embodiment, a piezoelectric vibratingmembrane is provided to help facilitate dye solution formation. Inanother embodiment, a magnetic stirring device is provided. In otherembodiments, a motorized blade spins to facilitate dye formation. Insome embodiments, the current speed and/or direction of the dye solventhelps facilitate dissolution. The device to facilitate dye dissolutionmay be provided with the reservoir itself or at any other location influid communication with the dye reservoir.

For example, in some embodiments, the dye pellet, powder, or liquid isintroduced by changing the entire dye reservoir 514, or by adding thedye in the handpiece 530, the base unit 510, or in the umbilicus 540.For example, the dye may be packaged within a cartridge that is insertedinto a housing located within the handpiece 530, the base unit 510, orthe umbilicus 540. In some embodiments, a dye pellet can weigh less thana gram and can last for about or greater than 70,000 pulses in use whendissolved in a 1 liter solvent reservoir.

A listing of dyes, solvents, and additives useful with the presentinvention is provided in attached Appendix A. Certain dye solutions, forexample, water-based dyes, can be selected to result in a non-hazardoussolvent system that is at least one of non-flammable or non-toxic and soas to not require hazardous waste disposal of the solvent. In someembodiments, two or more dye pellets, powders, or liquids can be used sothat the circulating or passing dye solution includes a combination ofdyes. The dyes can be selected so that one or more of the dyes drive oneor more of the others. For example, one dye can be configured to absorblight from the light source and emit a wavelength of light that isbetter absorbed by another dye. In some embodiments, more than one dyecan be introduced into the solvent so that more than two peaks, orportions of more than two peaks, are emitted from the waveguide.

One embodiment of a dye removal system 700 is illustrated in FIG. 8. Thedye removal system 700 allows the user to quickly and safely, manuallyor automatically, remove the dye from the dye solution. Once removed,the dye may be manually or automatically replaced with the same or adifferent dye pellet, solution, powder, etc. For example, if a userdesires to change the therapeutic wavelength of light emitted from thefluorescing handpiece, the user may select a dye solution correspondingto the desired wavelength. In addition, if the user desires to changethe therapeutic wavelength, he or she may activate a control at a userinterface to cause automatic dye removal and replacement. A specific dyemay be selected to obtain a therapeutic light from the handpiece havinga specific, desired wavelength.

The dye removal system 700 is designed to direct the dye solution fromthe reservoir 514 to a dye removal device 710 upon user activation. Inone embodiment, the dye removal system 700 includes a bypass valve 712,such as a 3-way or 4-way valve. The bypass valve 712 includes first 714and second 716 inputs and first 718 and second 720 outputs. Dye solutionis received by the bypass valve 712 at its first input 714 and prior todye removal activation, is directly sent to the bypass valve's firstoutput 718. The dye solution is sent to the fluorescing handpiece fromthe bypass valve's first output 718.

However, when the user desires to change the wavelength of light emittedfrom the fluorescing handpiece or if the dye solution has lost itseffectiveness and needs to be changed, the user activates the dyeremoval system 700. When activated, dye solution is directed by thebypass valve 712 from the first input 714 to the bypass valve's secondoutput 720 and to a dye removal device 710. The dye removal device 710is configured to mechanically, electrically, magnetically, and/orchemically remove the dye from the dye solution. For example, in oneembodiment, the dye removal device 710 includes a deionization filterconfigured to remove dye ions from the dye solution. When dye ions areremoved from the dye solution, only substantially clear water remains inthe dye solution. The clear water is provided from the dye removaldevice 710 to the bypass valve's second input 716, from which it isdirected to the bypass valve's first output 718. From the first output718 the clear water circulates or passes through the entire dye solutionfluid loop (including through the handpiece), and is collected as clean,clear water in the base unit's reservoir 514. The bypass valve 712advantageously allows for the dye solution to be rerouted to the dyeremoval device without introducing air bubbles into the solution. Thebypass valve 712 further allows for removal of the dye outside the mainfluid loop so that only clean water is reintroduced into the main loopready to receive a new dye pellet, powder, or drops. In someembodiments, the dye solutions passes through the dye removal device 710more than once to more completely purge the dye from the solvent. Insome embodiments, the deionization filter can last for about or longerthan 20 years. In some embodiments, the deionization filter can last forabout or longer than 1 year.

In another embodiment, the dye removal device 710 includes a polarityfilter, for example, an activated carbon filter, configured to removepolar dye molecules from the dye solution. Because water is a polarmolecule, water (and other polar solvents) can dissolve both ionic andpolar molecules. However, a deionization filter cannot remove polar butnon-ionic molecules from the dye solution. In some embodiments, the dyeremoval system 700 is partially or entirely housed in a cartridgeconfigured to be removably coupled to the base unit 510 and/or handpiece530. This advantageously allows the user to select a dye removal system700 including the appropriate dye removal device 710, e.g., one or moreof a deionization filter, polarity filter, etc., for the particular dye(or dyes) to be removed from the dye solution. In some embodiments,multiple dye removal devices 710 of the same or different types can becoupled in series. In some embodiments, the valve 712 passes the dyesolution first through one dye removal device 710 and then through atleast one more dye removal device 712.

In some embodiments, the dye removal system 700 can function in atwo-step process. At least one compound can be added to the dye solutionto facilitate the removal of the dye by filtration. The dye solutionincluding the compound can then pass through the dye removal device 710.For example, in some embodiments, chelants can be added to the dyesolution. Chelants are chemicals that can form soluble, complexmolecules with, e.g., certain metal ions, forming a chelate complex andinactivating the ions. The chelants added can have a high affinity forthe dye molecules, ions, and/or polar molecules. Chelation can promotethe formation of clusters of ions or molecules, which can facilitatefiltering of the dye ions or polar dyes molecules. Other compounds canbe added to the dye solution in addition to or instead of chelants.

After a predetermined time period, e.g., 30, 60, 90, 120, 300, or 600seconds, substantially all of the dye has been removed from the dyesolution, and the user may add a different dye pellet, powder, or dropsto the reservoir 514 or anywhere else in the passage of dye solution inorder to change the therapeutic wavelength of light to be emitted fromthe fluorescing handpiece. In other embodiments, a sensor is included inthe dye solution flow path to detect the presence of dye within the dyesolution. For example, in some embodiments a color sensor is used. Whenthe sensor does (or does not) detect the color of the dye, the systemindicates that the dye has not (or has) been removed from the dyesolution. In some embodiments, a conductivity sensor can be used.

In other embodiments, a sensor includes an emitter that emits a lightabsorbed by the dye and a detector that detects the emitted light. Ifthe dye is present in the dye solution, the sensor will not detect theemitted light; otherwise, it will. Such a sensor may be used todetermine whether adequate dye removal has occurred such that a new dyemay be added.

In some embodiments, the bypass valve 712, as well as the tubing used tocarry the dye solution, is made from one or more of Delrin, PTFE, TUVand/or stainless steel. Other types of tubes, such as polyethylene tubescan sometimes release contaminating substances into the dye solution,which can destroy its usefulness as a fluorescing medium.

In some embodiments, the controller 522 can be programmed to allow forautomatic changing and/or refreshing of the dye. For example, a sensorcan detect when the dye drops below a certain density, concentration,color level, etc. and provide a control signal or input to thecontroller regarding the dye condition. The controller can thenautomatically cause more dye to be released into the solution from acartridge, reservoir, or another source. The controller can alsoautomatically cause dye of a different wavelength to be added to thereservoir solution. Mixing dyes of different colors can cause thefluorescing light to include two or more primary wavelengths. Inaddition, the controller can also automatically activate the valve 712to cause removal of the dye from the system. When the valve isactivated, the solution flow is routed through the filter, which removesthe dye from the solution. In some embodiments, the user can select frommultiple cartridges, reservoirs, bins, etc. containing different dyesvia a user interface, and the controller can then release the selecteddye into the solution. In some embodiments, the user may be able toprogram the controller to automatically remove the dye in the solutionand inject another dye after a certain period of time or when certainconditions are met.

One embodiment of a cooling system 750 is illustrated in FIG. 9. Thecooling system 750 is configured to cool the dye solution prior to orafter delivery to the fluorescing handpiece. The cooling system 750includes a cold plate 752, a hot plate 754, a thermocoupling 756 betweenthe cold plate 752 and the hot plate 754, and a heat exchanger 758. Thecold plate 752 includes a thermally conductive material having a flowpath into which the dye solution is directed. Heat from the dye solutionis carried by the thermally conductive material to the hot plate acrossa thermocoupling 756. In one embodiment, the thermocoupling 756 includesa thermoconductive paste. In another embodiment, the thermocoupling 756includes one or more, or an array of thermoelectric coolers. Thethermoelectric coolers help draw the heat out of the dye solution andinto the hot plate 754. The hot plate circulates a cooling fluid (e.g.,water, methanol, ethylene glycol, propylene glycol, etc.) in aclosed-loop system with a heat exchanger 758. In one embodiment, theheat exchanger 758 includes a radiator, pump, and a fan. Fluid from theradiator enters the hot plate 754 and is warmed by the heat absorbedfrom the cold plate 752 via the thermocoupling 756. The warm fluidcirculates back to the radiator where it is cooled as it flows throughthe radiator's cooling fins, which are cooled by air blown with the fan.

In one embodiment, the cooling system includes two or more hot plates.For example, in one embodiment, the cooling system includes one hotplate on opposite sides of the cold plate (see FIG. 8). Fluid circulatesthrough the second hot plate 754 b and through the heat exchanger 758,as described above. In one embodiment, the cooling system cools the dyesolution to about 1° C., 5° C., 10° C., 14° C., or room temperature.

In one embodiment, the power supply 520 is an electrical networkconfigured to deliver electrical energy to drive the electromagneticenergy source 532 located within the handpiece 530. For example, in someembodiments, the power supply 520 includes one or more of a high-voltagepower supply, capacitor, inductor, battery, autotransformer, energystored as kinetic energy and released as electrical energy, energystored as chemical energy and released as electrical energy, pulseforming network, switching components, IGBT transistor, MOSFET, etc.

In one embodiment, the controller 522 includes a microprocessorconfigured to drive the electromagnetic energy source, for example, byactivating and deactivating the components of the power supply. Thecontroller 522 may also include a user interface, such as a controlpanel and/or graphical user interface.

One embodiment of a handpiece 800 is illustrated in FIG. 10. Thehandpiece 800 includes an electromagnetic energy source assembly 810 anda waveguide assembly 820. The electromagnetic energy source assembly 810is shown as a flashlamp 812 enclosed within a flow tube 814. A coolingfluid enters the flow tube 814 at an input port 816, circulates aroundthe flashlamp 812, and exits the flow tube 814 at an exit port 818.Light emitted from the flashlamp 812 is directed to a waveguide assembly820. The waveguide assembly 820 may include a separate housing, or maybe integrally formed with the flashlamp's flow tube 814.

In addition, the electromagnetic energy source may include any of avariety of optical devices, including but not limited to: an arc lamp, aXenon arc lamp, a Krypton arc lamp, a Xenon-Krypton arc lamp, aflashlamp, a Xenon flashlamp, a Krypton flashlamp, a Xenon-Kryptonflashlamp, a laser, a frequency-doubled Nd:YAG laser, a diode laser, afiber laser, a fiber delivered laser, a dye laser, a Ruby laser, anAlexandrite laser, and/or a laser pumped laser.

In one embodiment, also shown in FIG. 10, the handpiece's waveguideassembly 820 includes a waveguide 822 and an output optic 824. In oneembodiment, the output optic 824 includes a sapphire rod. In otherembodiments, the output optic 824 can be a glass, for example, BK7glass. Other materials are also possible. The waveguide 822 and outputoptic 824 are enclosed within a housing 826. Dye solution from the baseunit enters the housing 826 at an input port 828, flows through thewaveguide 822, and exits the housing 826 at an output port 830. Thewaveguide 822 and rod 824 are held in position within the housing 826with o-rings 832. In addition, in the embodiment illustrated in FIG. 9,the output optic 824 (e.g., rod) has an optical input face 834 that isclose to the housing's output port 830. Dye solution flows across andcools the rod's input face 834, but does not flow along the rod's axiallength.

However, in the embodiment illustrated in FIG. 11, an alternatewaveguide assembly 850 includes an output optic 854 positioned within alonger housing 856 to allow dye solution to flow around and cool alarger area of the rod 854. For example, the rod's input face 864 isproximally positioned with respect to the housing's output port 860 tocreate a rod cooling segment 870. In some embodiments, the rod coolingsegment 870 is 40-50 mm long, and the entire rod length 854 is about 100mm. The longer cooling segment 870 results in better contact cooling ofthe skin.

In addition, in some embodiments, the output optic is covered around itscircumference with an optically-insulating coating, such as Teflon (PTFEAF-2400) or another material having a lower refractive index than theoutput optic. The Teflon coating has a refractive index that allows itto act as a cladding around the rod, which increases optical efficiency.In addition, the Teflon coating optically isolates the o-rings from therod, which prevents optical leakage from the rod at the points where therod would otherwise contact the o-rings. In some embodiments, the outputoptic is coated with a reflective material such as silver, gold, or anoptical coating, i.e., having at least one layer of a dielectricmaterial.

The same benefit may be obtained by using a waveguide having a highrefractive index and cladding it with Teflon (or a similar insulator)around the areas in contact with the o-rings. In another embodiment, atleast one of the o-ring areas of the waveguide is coated with areflective material such as silver, gold, or an optical coating. In suchan embodiment, the difference in indices of refraction between theo-rings and waveguide may not significantly affect the optical efficacyor protection of the o-rings. In some embodiments without a coating onthe waveguide 110, the o-rings can be coated with PTFE or another lowrefractive index material to help minimize the loss of light leakinginto the o-rings and to help protect the o-rings. The same or a similaro-ring arrangement can be used on the output optic 824 when the outputoptic 824 does not include a coating at the site of the o-rings.

In some alternative embodiments, the waveguide can be a substantiallysolid rod rather than a pipe having a passage for circulation or passingof a fluorescent substance. The waveguide can be, for example, a crystalor glass hosting an ion or ions. The solid waveguide can comprise, forexample, fluorescent glass such as a Lumilass glass, e.g., Lumilass G9,available from Sumita, a solid state fluorescent medium, titanium-dopedsapphire, ruby, erbium-doped YSGG, erbium-doped YAG, neodymium-dopedYAG, chromium-doped crystal, or Alexandrite. In some embodiments, thewaveguide can comprise a polymer doped with a second fluorescent dye,which absorbs photonic energy from the source and transfers the energyto the fluorescent material, thereby increasing fluorescence efficiencyof the system. The handpiece can still only require a single reflector170 opposite the handpiece output rather than two opposing mirrors as ina laser system. In some embodiments, a dye solution flows over and/oraround the solid waveguide to cool the waveguide and to help produceextra energy to drive the rod.

In some embodiments, a flow jacket, e.g., a crystal, glass, or polymertube can surround at least part of the waveguide. A gap between thewaveguide and flow jacket can allow for the circulation of a temperatureconditioning (e.g., cooling, heating, or stabilizing) liquid or gas overa portion of the waveguide. In some embodiments, the circulating liquidor gas can include at least one fluorescent material. The circulatingliquid or gas can at least partially absorb light from the source andemit light at least partially absorbed by the fluorescent material inthe waveguide or optional dopant in the waveguide. The circulatingliquid or gas can also or alternatively emit light to be delivered tothe biological tissue.

In some embodiments, the handpiece can include a selector capable ofselecting for either light emitted from the waveguide or fluidcirculating between the waveguide and flow jacket. In some embodiments,the selector selects for a fractional combination of light emitted bythe waveguide and circulating fluid. The selector can be, for example,an optical filter, prism, coating, geometrical optical shape, or anyother wavelength attenuating or wavelength selective optical component.The selector can be located anywhere along or surrounding the waveguide,output optic, skin contacting portion if present, or anywhere inbetween.

In some embodiments, the flow jacket can contain at least onefluorescent material. The flow jacket can absorb at least part of lightemitted from the source and emit light that is delivered to the tissueand/or absorbed by the waveguide and/or the fluorescent circulatingfluid. Light emitted by the fluorescent circulating fluid can in turn bedelivered to tissue and/or absorbed by the waveguide. A selector canselect for one of or a combination of light emitted by the flow jacket,waveguide, and/or circulating fluid.

As described herein, the waveguide 110 can be adapted to deliverelectromagnetic radiation to skin 920 through a skin contacting portion140 or output optic 854 adjacent the waveguide 110. The skin contactingportion 140 or output optic 854 can include, for example, a glass,silica, sapphire, or plastic. Direct contact with the skin 920 may benecessary due to scatter and total internal reflection that occurs at aboundary between the output optic 854, e.g., sapphire rod, and air whenthere is an air gap 910 between the output optic 854 and skin 920 asshown in FIG. 12. Different materials have different refractive indices.When light traveling through one material strikes a boundary withanother material having a lower refractive index, the difference inrefractive indices can cause a portion of the light to travel into thesecond material and a portion of the light to be reflected back into thefirst material. The difference in refractive indices can also causerefraction (change in the angle of propagation) of the light allowedinto the second material. If the light strikes the boundary at an anglerelative to normal that is greater than the critical angle (i.e., closerto being parallel to the boundary plane), all of the light is reflectedback into the first material and none passes into the second.

When there is an air gap 910 between the output optic 854 and skin 920,the light must cross the output optic 854-air boundary and the air-skin920 boundary. Because the output optic 854, e.g., sapphire, typicallyhas a higher refractive index than air, a portion of light that impactsthe output optic 854-air boundary at an angle of incidence less than thecritical angle will be refracted and a portion will be reflected, asillustrated by ray 1 in FIG. 12. Light that impacts the boundary at anangle greater than the critical angle, e.g., angle θ in FIG. 12, will betotally reflected within the output optic 854 and none will cross theair gap 910, as illustrated by ray 2 in FIG. 12. Therefore, too muchlight can be lost when the light must travel first through air beforereaching the skin. For example, in some cases about one-third of thetotal light reaches the skin 920.

In some embodiments, however, the output optic 854 can be adapted todeliver electromagnetic radiation directly to the skin 920 withouthaving to directly contact the skin 920, or to deliver electromagneticradiation closer to perpendicular to the skin when in direct contactwith the skin 920. The output optic 854 can include a flare 900, forexample, as shown in FIG. 13, to form a lens system. The flare 900 canbe, for example, a cylindrical flare or a truncated pyramid. The flare900 can help change and control the angle of light traveling through theoutput optic 854 and reaching the boundary with air or a contact mediumto help keep the angle of incidence less than the critical angle andreduce total internal reflection. In some embodiments, the flare 900 canincrease the spot size from about 8 mm to about 16 mm. In someembodiments, the flare 900 can increase the spot size to, for example,about 10 mm, about 15 mm, about 20 mm, about 25 mm, about 30 mm, about35 mm, or about 40 mm. In some embodiments, the flare 900 can allow forabout 95% of the light to reach the skin 920. The output optic 854 canbe tapered or flared over its entire length, or only over a portionthereof, for example, as shown in FIG. 13. The flare can be ground,cast, machined or formed by any other appropriate method. In someembodiments, a tapered or flared tip can be removably attachable to theremainder of the output optic 954 via a coupling 930. A detachable tipcan advantageously allow for easier sterilization between uses or can bedisposable and replaceable between uses. Such a non-contact system canallow for an air gap 910 between the handpiece and skin 920 in use,which can advantageously allow the user to monitor the skin duringtreatment, for example, to ensure the treatment is working and/or towatch for adverse reactions. The non-contact system can also allow theuser to avoid pressing blood out of the underlying vessels bycompressing the skin 920. In some embodiments, an output optic to skincoupling substance can be applied to the skin 920 or end of the outputoptic 920 before or during treatment to, for example, enhance treatmentlight coupling to the tissue and/or inhibit adverse effects. Forexample, a gel, water, oil, silicone oil, fat, and/or petroleum jellycan be applied to the skin 920.

While the invention has been particularly shown and described withreference to specific embodiments, it should be understood by thoseskilled in the art that various changes in form and detail may be madewithout departing from the spirit and scope of the invention as definedby the appended claims.

APPENDIX A

Dyes, solvents and additives that may be used in combination to form dyesolutions in accordance with various embodiments include, but are notlimited to:

Water soluble dyes which may be used alone or in combination include butare not limited to:

Solubility Dye grams/liter labs¹ (nm) lfl (nm) IR 125 1.4-3^(w),678^(w), 800^(w/LO), 795^(s) 833^(s) soluble^(m) HITC Special 2.1^(w),soluble^(m) 741^(w), 757^(w/LO) ~743^(e), 751^(s) Oxazine 750 ~2.3^(w),~50^(m) 662^(m) 678^(m) Chloride Oxazine 725 ~3.1^(w), soluble^(m)645^(e) 680^(e) Chloride Oxazine 720 ~17^(w), soluble^(m) 627^(e)650^(e) Chloride Sulforhodamine ~1^(w), 34^(m) 576^(e),586^(w or w/LO 1) 602^(e) 640 Kiton Red 620 92^(w), 158^(m) 554^(e),566^(w or w/LO) 575^(e) Rhodamine 590 4.8^(w), 665^(m) 530^(e) 560^(e)Chloride Pyrromethene 6^(w), 0.74^(m) 492^(m), 490.6^(w) 533^(m) 556Disodium soluble^(w,m) 501^(e) 531^(e) Fluorescein Silbene 420 34^(w),14^(m) 349^(m) 425^(e(402,450sh))

General fluorescent dyes which may be used alone or in combinationinclude but are not limited to:

Laser Dye Laser Dye Laser Dye DMQ Coumarin 478 Rhodamine 610 QUICoumarin 480 Tetrafluoroborate TBS Coumarin 481 Rhodamine 610 DMTCoumarin 485 Perchlorate p-Terphenyl Coumarin 487 Kiton Red 620 TMQ LD489 Rhodamine 640 BPBD-365 Coumarin 490 Perchlorate PBD LD 490Sulforhodamine PPO Coumarin 498 640 p-Quaterphenyl Coumarin 500 DODCIodide Exalite 377E Coumarin 503 DCM Exalite 392E Coumarin 504 DCMSpecial Exalite 400E (Coumarin 314) LD 688 Exalite 348 Coumarin 504T LDS698 Exalite 351 (Coumarin 314T) LDS 720 Exalite 360 Coumarin 510 LDS 722Exalite 376 Coumarin 515 LDS 730 Exalite 384 Coumarin 519 LDS 750Exalite 389 Coumarin 521 LDS 751 Exalite 392A Coumarin 521T LDS 759Exalite 398 Coumarin 522B LDS 765 Exalite 404 Coumarin 523 LDS 798Exalite 411 Coumarin 525 LDS 821 Exalite 416 Coumarin 535 LDS 867Exalite 417 Coumarin 540 Styryl 15 Exalite 428 Coumarin 540A LDS 925 BBOCoumarin 545 LDS 950 LD 390 Pyrromethene 546 Phenoxazone 660 a-NPOPyrromethene 556 Cresyl Violet 670 PBBO Pyrromethene 567 Perchlorate DPSPyrromethene 567A Nile Blue 690 BBO Pyrromethene 580 Perchlorate POPOPPyrromethene 597 LD 690 Bis-MSB Pyrromethene 597-8C9 PerchlorateStilbene 420 Pyrromethene 605 LD 700 LD 423 Pyrromethene 650 PerchlorateLD 425 Fluorescein 548 Oxazine 720 Carbostyryl 165 Disodium FluoresceinPerchlorate Coumarin 440 Fluorol 555 Oxazine 725 Coumarin 445 Rhodamine3B Perchlorate Coumarin 450 Perchlorate HIDC Iodide Coumarin 456Rhodamine 560 Oxazine 750 Coumarin 460 Chloride Perchlorate Coumarin 461Rhodamine 560 LD 800 LD 466 Perchlorate DOTC Iodide LD 473 Rhodamine 575DOTC Rhodamine 19 Perchlorate Perchlorate HITC Rhodamine 590 PerchlorateChloride HITC Iodide Rhodamine 590 DTTC Iodide Tetrafluoroborate IR 144Rhodamine 590 IR 125 Perchlorate IR 143 Rhodamine 610 IR 140 Chloride IR26 DMOTC

Solvents which may be used alone or in combination include but are notlimited to: Water, ethanol, methanol, glycol, glycerol, ethylene glycol,propylene glycol, propylene carbonate, acetone (low polar solvent),DMSO, benzene, benzyl alcohol, toluene, diesel, 9-Methylanthracene (nonpolar solvent), dimethylsulfoxide.

Additives which may be used alone or in combination include but are notlimited to: COT cyclo-octo-tetraene (tripplet quencher), Amonyx LO(detergent), azeotropic amounts of a second solvent, saturableabsorbers, fluorescent dye modelocking saturable absorbers.

Saturable absorbers which may be used alone or in combination includebut are not limited to:

Saturable Absorber BDN Cryptocyanine DASBTI DASPI DCI′ DDBCI DDI DIDMETCI DNTTCI DOCI DODCI DOTCI DQOCI DQTCI DQTCI′ DQTrCI DTCI DTDCI DTPHDITCP HICI HIDCI HITCI IR-140 IR-143 Malachite Green NCI PICIPinacyanol Q-Switch I Q-Switch 5 Saturable Absorber 580

Fluorescent dye modelocking saturable absorbers which may be used aloneor in combination include but are not limited to:

DASPI 04620 DQTCI 06220 DOCI 05410 DASBTI 05360 DQTCI′ 06240 HICI 05670DOCI 05410 DTDCI 07310 DASBTI 05360 DMETCI 05240 Cryptocyanine 07070DQOCI 05920 PICI 05200 DDI 08100 DQOCI + DODCI DQOCI 05920 DOTCI 0825005920 + 06480 Pinacyanol 05940 IR-140 09500 DODCI 06480 DODCI 06480 DI05235 DODCI + Malachite Green 06480 + 20100 DDI 08100 DODCI 06480Saturable Absorber 580 HITCI 08422 DQTCI 06220 05800 NCI 07730 DQTCI′06240 Cresyl Violet 06700 DASPI 04620 DTDCI 07310 DQTCI 06220 DASBTI05360 Cryptocyanine 07070 DCI′ 05950 DOCI 05410 DDI 08100 DOTCI 08250DMETCI 05240 DOTCI 08250 DOTCI + DCI 08250 + PICI 05200 IR-140 0950007070 DQOCI 05920 Cryptocyanine 07070 Pinacyanol 05940

What is claimed is:
 1. A light-emitting, therapeutic system configuredto treat biological tissue, comprising: a source of electromagneticradiation; a waveguide positioned to receive electromagnetic radiationfrom the source, the waveguide comprising: first and second ends, and awall extending therebetween, the wall configured to at least partiallytransmit the electromagnetic radiation therethrough, the wall defining apassage extending along a direction between said first and second ends;a fluorescent substance flowable within the passage, the fluorescentsubstance comprising a liquid base and a fluorescing agent; and an firstport and an second port in fluid communication with the passage; anoptical output element near one of the first and second ends of thewaveguide; wherein the fluorescent substance is configured to absorb atleast a portion of the electromagnetic radiation from the source throughthe wall and generate fluorescent light in response to theelectromagnetic radiation, wherein the waveguide is configured to guidethe fluorescent light emitted by the fluorescent substance towards theoptical output element by internally reflecting at least a portion ofthe fluorescent light, and wherein the optical output element isconfigured to direct at least a portion of the fluorescent light towardsbiological tissue; a fluid conduit in fluid communication with the firstand second ports and configured to carry the fluorescent substancebetween the waveguide's passage and a fluid moving system, the fluidmoving system adapted to move the fluorescent substance from the firstend to the second end through the passage and from the second end backto the first end through the fluid conduit; and a polarity filterconfigured to be coupled to the fluid conduit and to remove thefluorescing agent from the fluorescent substance, the fluid conduitbeing configured to direct the fluorescent substance through thepolarity filter during a first mode of operation and to bypass thepolarity filter during a second mode of operation.
 2. The therapeuticsystem of claim 1 wherein a spectrum characterizing the fluorescentlight delivered to the biological tissue is matched to an absorptionspectrum of at least one of melanin, porphyrin, exogenous pigment, fat,and water in the biological tissue.
 3. The therapeutic system of claim1, wherein the fluorescent substance further comprises an additive. 4.The therapeutic system of claim 3, wherein the additive is selected froma group consisting of one or more of the following: a solubilityenhancing agent, a passive absorber, a fluorescent dye lifetimeenhancing agent, a detergent, or a substance configured to change thepolarity of the fluorescent substance.
 5. The therapeutic system ofclaim 3, wherein the additive is configured to change a property of thefluorescent substance, wherein the property is selected from a groupconsisting of one or more of the following: absorption wavelengthbandwidth, absorption wavelength bandwidth position in theelectromagnetic spectrum, emission wavelength bandwidth position in theelectromagnetic spectrum, emission wavelength bandwith, absorption peakwavelength, emission peak wavelength, absorption efficacy, emissionefficacy, Stokes shift, fluorescent dye lifetime, proticity, whethersolution is more or less protic or aprotic, whether solution will let goof hydrogen bound to primarily oxygen in a solution, or polarity offluorescent substance.
 6. The therapeutic system of claim 3, wherein thefluorescing agent removal device is further configured to remove theadditive from the fluorescent substance.
 7. The therapeutic system ofclaim 1, further comprising the fluid moving system, wherein the fluidmoving system is configured to pump the fluorescent substance throughthe waveguide in a first mode from the first port to the second port andin a second mode from the second port to the first port.
 8. Thetherapeutic system of claim 1, wherein the fluid moving system isconfigured to reverse the flow of the fluorescent substance through thefluid conduit in response to a fluid flow control signal.
 9. Thetherapeutic system of claim 1, wherein the fluorescing agent comprisestwo or more dyes and the fluorescent light comprises two or moreemission peaks.
 10. The therapeutic system of claim 9, wherein at leasttwo of the emission peaks at least partially overlap.
 11. Thetherapeutic system of claim 1, further comprising a handpiece, wherein acooling system is located within the handpiece.
 12. The therapeuticsystem of claim 1, wherein the optical output element is selected fromthe group consisting of one or more of the following: a spacer, apositive tapered waveguide, a negative tapered waveguide, a waveguidehaving different surface areas at its proximal and distal ends, awaveguide having different shapes at its proximal and distal ends, abifurcated waveguide, a multi-furcated waveguide, a fiber bundle, afiber bundle having a larger surface area at its output end than at itsinput end, a plurality of apertures, an aperture, a solid light guide, aliquid light guide, a hollow light guide, and a fiber.
 13. Thetherapeutic system of claim 1, further comprising a solid rod locatedwithin the waveguide, the sold rod configured to generate fluorescentlight in response to the electromagnetic energy.
 14. A method oftreating biological tissue, comprising: providing a light-emittingsystem adapted to treat biological tissue, said light-emitting systemcomprising: a waveguide positioned to receive electromagnetic energyfrom an electromagnetic energy source, the waveguide comprising: firstand second ends, and a wall extending at least partially therebetween,the wall configured to transmit the electromagnetic radiationtherethrough and defining a passage extending along a direction betweensaid first and second ends; a fluorescent substance flowable within thepassage, the fluorescent substance configured to absorb theelectromagnetic radiation and generate fluorescent light in response tothe electromagnetic radiation, the fluorescent substance comprising aliquid base and a first fluorescing agent; and an input port and anoutput port in fluid communication with the passage; an optical outputelement near one of the first and second ends of the waveguide; a fluidconduit in fluid communication with the input and output ports; movingthe fluorescent substance from the first end to the second end throughthe passage and from the second end back to the first end through thefluid conduit; transmitting electromagnetic radiation through the wallof the waveguide to the fluorescent substance within the passage;guiding at least some of the fluorescent light emitted by thefluorescent substance in response to the electromagnetic radiationthrough the waveguide towards the optical output element, thefluorescent light having a first peak wavelength; removing thefluorescing agent from the fluorescent substance by directing thefluorescent substance through a fluorescing agent removal device; andproviding a second fluorescing agent to the liquid base after saidremoving, the second fluorescing agent being different than the firstfluorescing agent.
 15. The method of claim 14, wherein the secondfluorescing agent is configured to generate light having a second peakwavelength that is different from said first peak wavelength.
 16. Themethod of claim 14, wherein said removing comprises directing thefluorescent substance through one of a deionization filter or a polarityfilter.
 17. The method of claim 14, wherein the providing an additionalquantity of the fluorescing agent comprises adding a tablet, pellet,powder, or solution of dye to the liquid base.
 18. The method of claim14, wherein said providing comprises manually adding the fluorescingagent to the liquid base.
 19. The method of claim 14, further comprisingsensing a depletion of the fluorescing agent and activating an indicatorin response to said sensing.
 20. The method of claim 14, furthercomprising receiving an input to change the wavelength of thefluorescent light and performing said removing and providing a secondfluorescing agent in response to said input.